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Biomedical subjects

Elizabeth M Byrnes

Publications and source records attributed to Elizabeth M Byrnes.

10 recordsLinked to original sources

Sensorimotor gating and dopamine function in postpartum rats.

There is much speculation regarding the effects of estrogen withdrawal at the end of pregnancy on forebrain dopamine, however, few studies have directly examine changes in this system postpartum. The present work sought to determine what changes in forebrain dopamine function occur in the postpartum rat. Specifically, prepulse inhibition of the acoustic startle response (PPI) was measured in primiparous female rats on postpartum day 2 (PPD2) or 14 (PPD14) following treatment with saline or the dopamine D2 agonist, quinpirole. Diestrus (DI) females served as controls. Dopamine content and turnover as well as cyclic AMP (cAMP) accumulation were determined within the nucleus accumbens and dorsal striatum in these same females. In addition, circulating levels of plasma corticosterone, estradiol and progesterone were measured. PPI was significantly disrupted in both postpartum groups. This effect was associated with decreased cAMP content within the nucleus accumbens. Quinpirole treatment (0.1 and 0.5 mg/kg) dose-dependently disrupted PPI in DI controls while PPD2 and PPD14 animals demonstrated reduced sensitivity to the D2 agonist. PPD14 animals demonstrated increased startle amplitude, an effect that was attenuated by quinpirole treatment. PPD14 females were also less sensitive to quinpirole-mediated reductions in DA turnover within the nucleus accumbens and both PPD2 and PPD14 females had an attenuated response to the stimulatory effects of quinpirole on corticosterone secretion. Collectively these findings suggest that the postpartum period is associated with reduced sensorimotor gating and altered forebrain DA systems, which may be related to shifts in circulating hormones.

Animals↗

Reproductive experience reduces the sedative, but not anxiolytic effects of diazepam.

Benzodiazepines are frequently prescribed to women for both their anxiolytic and hypnotic effects. Previous studies in rodents have demonstrated reproductive experience, i.e. pregnancy and lactation, can alter sensitivity to certain drugs, such as morphine. The purpose of the present study was to determine whether reproductive experience alters sensitivity to the benzodiazepine, diazepam. Two groups of subjects were generated, a primparous group (pregnancy+21 days of lactation) and an age-matched, nulliparous group. All subjects were injected with diazepam (0.0, 0.5, 2.0 or 2.5 mg/kg) at least 6 weeks after primiparous females weaned their litters. Twenty minutes post-injection, subjects were place in an activity chamber and locomotor behavior was measured. Thirty minutes post-injection, subjects were tested on an automated elevated plus maze. In addition to behavioral testing, diazepam's effects on corticosterone levels were measured. Overall, diazepam's sedative effects on locomotor activity were significantly reduced in primiparous females when compared to nulliparous controls as determined both in the activity chamber and on the elevated plus maze. There was, however, no significant effect of reproductive experience on the anxiolytic effects of diazepam in the elevated plus maze. Finally, while diazepam increased corticosterone in both groups, primiparous females were less sensitive to the effects of the drug on corticosterone secretion. These results indicate that the effects of diazepam on locomotor activity and corticosterone secretion are attenuated following reproductive experience.

Animals↗

Reproductive experience alters anxiety-like behavior in the female rat.

Reproductive experience (i.e. pregnancy and lactation) results in significant alterations in subsequent hormone levels in female rats. Several studies have demonstrated that circulating hormones can significantly affect anxiety-like behavior. Thus, the purpose of the present study was to determine whether reproductive experience induces alterations in anxiety-like behaviors in cycling female rats and in older, reproductively senescent rats. In Experiment 1, the elevated plus maze (EPM) was used to test young cycling (6-8 weeks post-weaning) and middle-aged (32-36 weeks post-weaning) primiparous rats and their age-matched nulliparous counterparts for anxiety-like responses. In Experiment 2, activity in the open field was used as an additional measure of anxiety-like behavior in young (proestrus) and middle-aged (constant estrus) primiparous and nulliparous rats. For Experiment 3, EPM testing was conducted in separate groups of young and middle-aged animals tested two weeks after ovariectomy. The results revealed that during proestrus, primiparous animals exhibited fewer anxiety-like behaviors on the EPM compared to nulliparous controls. In middle-aged animals, however, parity was associated with increased anxiety-like behavior. In the open field, young, non-lactating primiparous animals again exhibited fewer anxiety-like behaviors compared to nulliparous controls, an effect that was reversed in middle-aged animals. Effects of reproductive experience on the EPM in both age groups were eliminated by ovariectomy. Overall, the findings indicate that reproductive experience significantly alters anxiety-like behavior, effects that are influenced by the endocrine status and/or age of the female.

Age Factors↗

Reproductive experience reduces circulating 17beta-estradiol and prolactin levels during proestrus and alters estrogen sensitivity in female rats.

The reproductive experiences of pregnancy, parturition, and lactation affect a range of neural and endocrine processes after the end of lactation. In women, previous parity results in reduced circulating prolactin (PRL) and androgen levels years after giving birth. Reductions in PRL secretion also occur in reproductively experienced, female rats. In the present study we examined the status and regulation of estradiol (E(2)) and PRL during the reproductive cycle after reproductive experience. These hormones regulate one another and have been implicated in a number of disease and aging processes. Using a rat model, the patterns of E(2) and PRL secretion, pituitary PRL content, and estrogen receptor alpha expression were characterized from 1200-1800 h on proestrus in age-matched, primiparous and nulliparous animals. The possible effect of parity on estrogen sensitivity was then examined by challenging nonlactating, ovariectomized, age-matched, multiparous and nulliparous rats with estradiol benzoate (EB; 0, 1, 5, 25, and 125 microg/kg) and measuring PRL responses 24 and 48 h later. Previous parity resulted in modest, yet significant, reductions in E(2) and PRL levels on proestrus, a limited increase in pituitary estrogen receptor alpha expression, and a significant shift in estrogen sensitivity, as measured by EB-induced PRL secretion. Nulliparous animals were more sensitive than multiparous rats to the two lower doses of EB, whereas multiparous animals were more responsive to the highest EB dose. These unique parity-induced alterations in the female's endocrine state that persist beyond lactation may impact a multitude of estrogen-mediated processes over the female's adult life span.

Animals↗

Reproductive experience and activation of maternal memory.

The maternal and neurobiological responses of biological mothers and pup-induced maternal virgin rats were compared 55 and 80 days after an initial 2-day maternal experience. When tested for home cage responsiveness after prolonged isolation from young, the biological, primiparous rats displayed shorter maternal latencies. Primiparous females tested in the presence of pups on the elevated plus-maze displayed increased exploration of the open arms and increased c-Fos expression in the cortical nucleus of the amygdala. Pup exposure and parity also enhanced activation of the nucleus accumbens shell and medial nucleus of the amygdala, respectively. Therefore, although both nulliparous and primiparous rats retain a maternal memory for a prolonged time, the memory and neurochemical response appear stronger in primiparous mothers.

Amygdala↗

Transgenerational consequences of adolescent morphine exposure in female rats: effects on anxiety-like behaviors and morphine sensitization in adult offspring.

RATIONALE AND OBJECTIVE: Opiate abuse in adolescent girls has increased in the past decade; however, few animal studies have examined the potential consequences of opiate use occurring at this time. The purpose of the present study was to determine whether exposing female rats to morphine during the peripubertal period can alter the adult behavior of their offspring. METHODS: Beginning at 30 days of age, female rats were injected subcutaneously (s.c.) twice daily with either morphine sulfate or saline. The initial morphine dose of 2.5 mg/kg was increased by 2.5 mg/kg daily for a total of 20 days. Ten days after the final drug treatment, all subjects were mated. Their subsequent offspring were then tested as adults on the elevated plus maze, in a novel environment or were examined in a morphine locomotor sensitization paradigm. RESULTS: Adult female offspring of dams exposed to morphine during puberty spent less time in the open arms of the elevated plus maze and displayed decreased exploration in a novel environment. Female offspring also demonstrated a more rapid induction of morphine sensitization. Finally, male offspring demonstrated a significant enhancement in the expression of morphine sensitization. CONCLUSIONS: Chronic morphine exposure during adolescence can have significant transgenerational effects on adult offspring. Future studies will be needed to determine how these changes are transferred to the offspring and whether these effects are specific to drug exposure that occurs during the peripubertal period.

Analysis of Variance↗

Chronic morphine exposure during puberty decreases postpartum prolactin secretion in adult female rats.

Opiate use in teenage populations has been increasing in recent years. The potential impact of exposure to high levels of opiates at a time when reproductive systems are maturing has not been well studied, especially in females. The present study used an animal model of adolescent opiate abuse in females to examine the potential impact of high levels of opiates during puberty on several reproductive parameters, including suckling-induced prolactin secretion. Two groups of juvenile female rats were administered increasing doses of morphine sulfate or saline (s.c.) from age 30-50 days, beginning with a dose of 2.5 mg/kg and achieving a maximal dose of 50 mg/kg. As adults, these females were mated and reared either their own or foster pups. On either postpartum day 5 or 10, following a 4 h separation, suckling-induced prolactin secretion was measured. In addition, on postpartum day 5 maternal behavior latencies were determined. The results demonstrate reduced suckling-induced prolactin secretion on postpartum day 5 in females previously exposed to morphine during pubertal development. These effects were observed in females rearing either their own or fostered pups. These effects were not due to any differences in maternal behavior latencies, as retrieval or crouching latencies were unaffected. In summary, chronic morphine exposure during puberty results in changes in the regulation of prolactin secretion during early lactation, which are observed several weeks after cessation of drug treatment. These data suggest that prior opiate use during puberty can continue to affect the regulation of prolactin secretion into adulthood.

Age Factors↗

Lactation reduces prolactin levels in reproductively experienced female rats.

Long-term alterations in prolactin (PRL) secretion following reproductive experience have been demonstrated in both women and female rats. In the rat, these changes include decreased PRL secretion in response to a dopamine antagonist challenge following ovariectomy, decreased post-coital diurnal and nocturnal prolactin surges in multigravid versus primigravid females, as well as decreased suckling-induced prolactin release in multiparous versus primiparous females. To date, there have been no studies examining PRL secretion following reproductive experience in cycling female rats. Studies in women, however, have demonstrated a reduction in basal PRL secretion during the menstrual cycle. The purpose of the present work was to determine whether similar changes occur in the rat during the estrous cycle and to what extent lactation is involved in these effects. In addition to examining PRL, potential parity-induced changes in estradiol secretion were also studied. The findings revealed a significant decrease in PRL levels during the afternoon of proestrus, which was only observed in primiparous females that had lactated. Significant differences in estradiol secretion were not detected following reproductive experience. Thus, a reduction in the PRL surge on the afternoon of proestrus is a consequence of reproductive experience that requires both pregnancy and lactation.

Analysis of Variance↗

Induction of maternal behavior in adult female rats following chronic morphine exposure during puberty.

The peripubertal period in the female rat is the time when the stimulatory effects of opioids on prolactin (PRL) secretion develop. In the adult rat, the administration of chronic high-dose morphine has been shown to attenuate the ability of opiates to stimulate PRL secretion. One function of PRL in adult virgin rats is the induction of maternal behavior. The present study examined whether chronic high-dose morphine exposure during the peripubertal period alters PRL-mediated induction of maternal behavior in adult female rats. Two groups of juvenile female rats were administered increasing doses of morphine or vehicle (s.c.) from age 30 to 50 days. As adults, these females either remained intact, or were ovariectomized and treated with a PRL-dependent, steroid hormone regimen that stimulates a rapid onset of maternal behavior. All females were then exposed daily to rat foster pups to determine whether peripubertal morphine exposure affected their latencies to induce maternal behavior. Morphine treatment resulted in a delay in vaginal opening and a temporary reduction in the rate of weight gain; however, the rate of onset of maternal behavior was unaffected by peripubertal morphine treatment. Thus, chronic morphine exposure in the pubertal female did not impact the expression of pup-induced maternal care.

Animals↗

Dopamine antagonists during parturition disrupt maternal care and the retention of maternal behavior in rats.

Brief contact with pups at parturition enables the female rat to establish and retain the full repertoire of maternal behaviors, allowing her to respond rapidly to pups in the future. To determine whether the dopamine system is involved in the retention of maternal behavior, females were continuously infused with dopamine antagonists during the periparturitional period and then allowed either a brief interaction period with pups (3 h) or no interaction with pups (pups removed as they were born). Females were exposed to either the D1-like antagonist SCH 23390 (0.1 or 1.0 mg/kg/day) or the D2-like antagonist clebopride (0.5 or 1.0 mg/kg/day). The high dose of either DA antagonist resulted in significant attenuation of maternal care immediately postpartum. When tested for the retention of maternal behavior 7 days later, however, only the females exposed to the D2 antagonist displayed a delayed response to shown full maternal behavior (FMB) towards donor pups. Thus, while both dopamine receptor subtypes appear necessary for the full and rapid expression of maternal behavior during the early postpartum period, only the D2 receptor subtype appears to be involved in the retention of this behavior.

Animals↗